We evaluated the effects of multiple fetal exposures to glucocorticoids on postnatal lung function and growth. Ewes were randomized to receive 1 to 4 doses of 0.5 mg/kg betamethasone or saline placebo at 7 d intervals from 104 d to 118 d and at 124 d gestation. All lambs were delivered preterm at 125 d gestation, and postnatal lung function was evaluated. There were sequential improvements in compliance, ventilation efficiency, and lung volumes for two, three, and four doses of betamethasone. The maximal effect was a 150% increase in compliance and a 4-fold increase in lung volume after fetal exposure to four doses of betamethasone. However, birth weights decreased (15% after one dose, 19% after two doses, and 27% after three and four doses). There were no changes in lung to body weight ratios, lung dry to wet weight ratios, lung protein to body weight ratios, or lung hyaluronan content. Prenatal glucocorticoid exposure also altered postnatal cortisol, thyroid, and catecholamine plasma levels. Repetitive 7-d interval exposures of fetal lambs to glucocorticoids progressively enhanced postnatal lung function and resulted in growth and endocrine abnormalities.

Repetitive prenatal glucocorticoids improve lung function and decrease growth in preterm lambs

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(06)68846-6.pdf

Neonatal respiratory distress syndrome after repeat exposure to antenatal corticosteroids: a randomised controlled trial

Modern neonatal practice has improved the outcome of extremely preterm infants. However, why some infants require prolonged periods of respiratory support while others improve after a short period of mechanical ventilation, remains largely speculative. Many risk factors, including barotrauma or volutrauma due to mechanical ventilation, oxygen toxicity, and infection, have been identified for the development of chronic lung disease of prematurity (CLD). Attempts to minimise these with modern neonatal practice, including newer ventilatory techniques, have had minimal impact on its incidence. Factors other than barotrauma and oxygen toxicity are likely to be important in the development of CLD.

Although our understanding of normal fetal lung development has increased substantially over the past few years, it nevertheless remains rudimentary, especially in infants who have survived neonatal intensive care. Animal models have provided many clues to the effects of interventions in the neonatal unit on the lung growth of preterm infants. Normal lung growth and some of the abnormalities that may result from disordered growth or from medical interventions are reviewed in this article. There are a vast number of other factors which influence lung growth—some, such as fetal breathing and lung fluid dynamics, deserve reviews of their own.

Normal lung development, which occurs as a series of complex tightly regulated events, can be divided into a number of stages (table1).1-3 During the earliest embryonic stage , the lung develops as an outgrowth of the ventral wall of the primitive foregut endoderm. Epithelial cells from the foregut endoderm invade the surrounding mesoderm to form the proximal structures of the respiratory tract. Following the formation of the trachea and the main bronchi, the five lobes are formed, and by the end of this stage, the 18 major lobules are recognisable. Current evidence suggests that the surrounding mesoderm regulates the branching …

https://fn.bmj.com/content/fetalneonatal/82/1/F69.full.pdf

Lung growth: implications for the newborn infant

Markers and mediators of inflammation in neonatal lung disease.

Very preterm infants have high rates of neurological impairments and disabilities. These rates have not diminished as the survival rates have improved. Basic science research suggests that magnesium sulphate before birth can be neuroprotective for the preterm fetus. Some, but not all, observational studies in humans also suggest a protective effect of antenatal magnesium sulphate on cerebral palsy. Four randomised controlled trials of antenatal magnesium sulphate have reported long-term neurological effects in surviving infants, but only one of these was designed specifically to evaluate the long-term effects of treatment. These studies found that, overall, antenatal magnesium sulphate therapy had no significant effect on paediatric mortality or neurological outcomes in the first few years of life, including cerebral palsy, but it was found to lower the rate of motor problems at 2 years of age in one study. The role for antenatal magnesium sulphate therapy as a neuroprotective agent for the preterm fetus is not yet established.

Antenatal magnesium sulphate neuroprotection in the preterm infant.

Australian Collaborative Trial of Antenatal Thyrotropin-Releasing-Hormone (Actobat) for Prevention of Neonatal Respiratory-Disease

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Australian Collaborative Trial of Antenatal Thyrotropin-Releasing-Hormone (Actobat) for Prevention of Neonatal Respiratory-Disease